Work in progress involves (1) chemical synthesis of lac operator DNA segments, (2) enzymatic joining of these segments to form the complete operator, and (3) studies on how this operator DNA interacts with lac repressor protein. Progress to date includes total synthesis of the operator DNA and several variable sequences. These variants include (1) operators with 5-bromodeoxyuridine in place of thymidine at specific sites, (2) insertion of modified nucleoside bases by DNA polymerase repair (e.g., deoxyuracil for thymine), and (3) site specific base pair changes resulting from chemical synthesis. These various operators have been studied for repressor binding activity. All bind repressor protein specifically and with variable lifetimes. Recent work includes insertion of these operators into the PMB9 plasmid. One objective of the plasmid work is to obtain large amounts of operator DNAs for various physical chemical studies. BIBLIOGRAPHIC REFERENCES: Studies on How Lac Repressor and lambda cl Repressor Interact with Their Respective Operator DNAs. M.H. Caruthers, E. Brand, T. Gadek, D.V. Goeddel, E. Kawashima and D.G. Yansura. Tenth International Congress of Biochemistry, Hamburg, July 25-31 (1976), Abstract 01-1-070. Synthesis of Lac and lambda Operator DNA Sequences. D.V. Goeddel, D.G. Yansura, E. Kawashima, T. Gadek, and M.H. Caruthers. Proceedings of the 1976 ICN-UCLA Conference on Molecular and Cellular Biology. In Press.